Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage

Abstract

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein.

Serum deprivation alters lipid profile in HN9.10e embryonic hippocampal cells

“…We have analyzed for the first time, the change of lipid profile in HN9.10e cells after serum deprivation by using UFLC-MS/MS systems, a methodology that allows to obtain simultaneous quantitative analysis of CHO, PC and sphingolipids [20]. Serum deprivation induces a decrease in CHO content to 48% of control samples (Fig.…”

“…The identification and analysis of CHO were conducted by atmospheric pressure chemical ionization (APCI) in positive ionization conditions and multipole ion scan modality as described in [20].…”

Radiation and Thyroid Cancer

“…In cell nuclei the strong activation of neutral-sphingomyelinase (N-SMase) reduced SM content that was important for the DNA-stability. The ceramide produced in the nucleus probably was translocated to the cytoplasm, where it could be metabolized to sphingosine and sphingosine-1-phosphate, lipid mediators involved in apoptosis [ 56 ].…”

Acid and Neutral Sphingomyelinase Behavior in Radiation-Induced Liver Pyroptosis and in the Protective/Preventive Role of rMnSOD

“…It was previously shown that in thyroid cells, ionizing radiation exposure induces proapoptotic signals via ceramide production from the SMs [19]. Moreover, proton beams move quiescent thyroid cells towards a proapoptotic state and proliferating thyroid cells towards an initial apoptotic state by altering the nuclear SM-metabolism [20]. In the same experimental model, ultraviolet radiation enriched the ceramide pool due to the ability of both aSMase and nSMase to induce apoptosis [21].…”

“…Our previous studies indicated that radiation targets SMase in the thyroid [20,21] and brain [22]. As there are two SMases involved in the apoptotic process (lysosomal aSMase and endoplasmic reticulum/nucleus nSMase1), we defined their behavior in the liver, where radiation upregulated Caspase-1, thereby triggering pyroptosis.…”